Teleost fish provide important models for understanding human health and disease. These include models for cancer and tumorigenesis, human development and infant health, cardiovascular disease, eye disease, bone disease, environmental toxicology, aging, and genome structure and regulation. Because teleost fish share a history of genome expansion, likely due to genome duplication, they often have 2 copies of single copy human genes. The partitioning of ancestral gene subfunctions between duplicated teleost gene copies facilitates analysis of ancestral gene functions shared with humans. The long-term objective of the proposed work is to provide resources related to duplicated teleost genes to greatly expand the utility of existing teleost models for human development, organ function, health, and disease. Aim 1 is to develop TelGen, software resources to automate the identification and phylogenetic analysis of duplicated genes in the sequenced genomes of teleost fish. Aim 2 is to use the new software to identify, investigate, and make publicly accessible in the TelGen2 database, the set of gene duplicates that arose in the proposed ray-fin genome duplication event. Aim 3 is to identify the most recently diverging, pre-duplication ray-fin lineage, and make available tangible genomic resources, including large insert genomic clones and cDNA libraries, and OldFish, a database for these sequences. Finally, Aim 4 is to create TelExDB, a resource of gene expression data for both copies of teleost duplicates of human disease genes, and to investigate general principles for the evolution of function in teleost gene duplicates. These resources and studies will improve connectivities and utility of teleost models by providing a general understanding of duplicate gene divergence across teleosts. In addition, they facilitate analysis in cases where the early essential function of a single copy mammalian gene obscures a later function. Analysis of duplicated teleost genes can ease discovery of candidate tissue-specific regulatory elements and protein structural motifs that may be targets for drugs with fewer side effects.